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HIV, Cytokines and Programmed Cell Death: A Subtle Interplay
Author(s) -
GOUGEON MARIELISE,
LEDRU ERIC,
NAORA HONAMI,
BOCCHINO MARIALUISA,
LECOEUR HERVÉ
Publication year - 2000
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2000.tb05596.x
Subject(s) - cytotoxic t cell , immune system , biology , immunology , cd8 , apoptosis , cytokine , microbiology and biotechnology , t cell , programmed cell death , biochemistry , in vitro
A bstract : HIV infection is marked by the progressive destruction of the CD4 T lymphocyte subset, an essential component of the immune system and a vital source of cytokines required for differentiation of natural killer (NK) and γδ T cells, for maturation of B lymphocytes into plasmocytes, and for differentiation of CD8 + T cells into virus‐specific cytotoxic T lymphocytes. CD4 T lymphocytes are also a source of chemokines which control migration of lymphocytes to the site of infection and which also inhibit HIV entry into CD4‐expressing targets. Continuous production of viral proteins leads to an unbalanced immune activation and to the triggering of apoptotic programs, turning mononuclear cells, including CD4 T cells, CD8 T cells and APC, into effectors of apoptosis, leading to fratricidal destruction of healthy uninfected cells expressing the death receptors. Inappropriate PCD is also responsible for the disappearance of T helper cells primed for type‐1 cytokine synthesis, thus contributing to the lack of survival factors which could prevent spontaneous lymphocyte apoptosis. Under potent anti‐retroviral therapies, a significant decrease in spontaneous, TCR‐ and CD95‐induced lymphocyte apoptosis is observed, concomitant with a partial quantitative and qualitative restoration of the immune system in treated patients. However, owing to the suppressive effect of anti‐retroviral drugs on physiological apoptosis, these therapies are associated with alteration of TNF‐α‐regulated T cell homeostasis, leading to an accumulation in the blood of T cells primed for TNF‐α synthesis, and contributing to the development of a new syndrome associated with these treatments, the lipodystrophy syndrome.